Gosset Molecular Classification
Peptide aggregate, Protein aggregate
Other Names
Aβ protofibril, Amyloid beta oligomers, Aβ oligomers
Disease Roles
Amyloid beta protofibril Overview
Amyloid beta (Aβ) protofibrils are intermediate, soluble aggregates formed during the self-assembly of amyloid beta peptides, particularly Aβ(1–40) and Aβ(1–42), which are central to the pathology of Alzheimer’s disease. These protofibrils represent a metastable state between smaller oligomers and mature amyloid fibrils. They are considered highly relevant as toxic species in neurodegenerative processes, disrupting cellular membrane integrity by inducing reactive oxygen species generation and lipid peroxidation. Compounds that stabilize or sequester Aβ peptides into non-toxic oligomeric or protofibrillar forms may have therapeutic potential if they prevent engagement with toxic pathways leading to cell damage or death.
Mechanism of Action
N/A
Biological Functions
Neurotoxicity
Membrane disruption
Reactive oxygen species generation
Lipid peroxidation
Amyloid fibril formation intermediate
Disease Associations
Alzheimer's disease
Neurodegenerative disease
Safety Considerations
- Targeting protofibrils without affecting beneficial Aβ functions
- Potential for off-target effects
- Ensuring drugs do not promote formation of more toxic species
Associated Biomarkers
| Biomarker |
|---|
| Levels of Aβ protofibrils in cerebrospinal fluid |
| Presence of Aβ protofibrils in brain imaging |